3-187744934-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001706.5(BCL6):c.-50+476G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,214 control chromosomes in the GnomAD database, including 825 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (825 hom., cov: 32)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

Genes affected

BCL6 (HGNC:1001): (BCL6 transcription repressor) The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal POZ domain. This protein acts as a sequence-specific repressor of transcription, and has been shown to modulate the transcription of STAT-dependent IL-4 responses of B cells. This protein can interact with a variety of POZ-containing proteins that function as transcription corepressors. This gene is found to be frequently translocated and hypermutated in diffuse large-cell lymphoma (DLCL), and may be involved in the pathogenesis of DLCL. Alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL6	NM_001706.5	c.-50+476G>C		intron_variant		ENST00000406870.7
LOC122526776	NR_173091.1	n.377-310C>G		intron_variant, non_coding_transcript_variant
BCL6	XM_047448655.1	c.-1081G>C		5_prime_UTR_variant	1/10
BCL6	XM_011513062.4	c.-50+476G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL6	ENST00000406870.7	c.-50+476G>C		intron_variant		1	NM_001706.5	P1
	ENST00000648485.2	n.360-310C>G		intron_variant, non_coding_transcript_variant
	ENST00000702512.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15169 AN: 152094 Hom.: 821 Cov.: 32

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0999 AC: 15199 AN: 152214 Hom.: 825 Cov.: 32 AF XY: 0.103 AC XY: 7651 AN XY: 74410

Gnomad4 AFR AF: 0.0629

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0806

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.0871

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0498 Hom.: 54

Bravo AF: 0.0974

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	18
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs80031434; hg19: chr3-187462722; COSMIC: COSV69202603;